A nuclear lncRNA Linc00839 as a Myc target to promote breast cancer chemoresistance via PI3K/AKT signaling pathway

• DOI: 10.1111/cas.14555
• Publication Date: 2020-07-03T15:38:19Z
• Authors: Qi Chen; Huiling Shen; Xiaolan Zhu; Yueqin Liu; Hui Yang; Hui Chen; Shangwan Xiong; Huamao Chi; Wenlin Xu
• Keywords: 0301 basic medicine; 0303 health sciences; Gene Expression Profiling; Genes, myc; Breast Neoplasms; Original Articles; Xenograft Model Antitumor Assays; 3. Good health; Gene Expression Regulation, Neoplastic; Disease Models, Animal; Mice; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; Drug Resistance, Neoplasm; Cell Line, Tumor; Animals; Humans; Female; RNA Interference; RNA, Long Noncoding; Proto-Oncogene Proteins c-akt; In Situ Hybridization, Fluorescence; Cell Proliferation; Signal Transduction

Abstract Chemoresistance has become a leading cause of mortality in breast cancer patients and is one the major obstacles for improving clinical outcome. Long noncoding RNAs play important roles tumorigenesis chemoresistance. However, involvement regulation lncRNAs chemoresistance are not completely understood. Here, we reported that Linc00839 was localized nucleus upregulated chemoresistant cells tissues, high level associated with poor prognosis. Knockdown significantly suppressed proliferation, invasion, migration, sensitized to paclitaxel vitro inhibited transplant tumor development vivo. Mechanistically, found Myc could directly bind promoter region activate its transcription. Furthermore, overexpression increased expression RNA‐binding protein Lin28B activated PI3K/AKT signaling pathway. We also discovered positively interacted tissues. Taken together, first time, showed by promoted proliferation through binding Lin28B. These findings provide new insight into regulatory mechanism propose Myc/Linc00839/Lin28B feedback loop be used as novel therapeutic target cancer.